Transfers between health facilities of people living with diabetes attending primary health care services in the Western Cape Province of South Africa: A retrospective cohort study.

OBJECTIVES: Transfers between health facilities of people living with HIV attending primary health care (PHC) including hospital to PHC facility, PHC facility to hospital and PHC facility to PHC facility transfers occur frequently, affect health service planning, and are associated with disengagement from care and viraemia. Data on transfers among people living with diabetes attending PHC, particularly transfers between PHC facilities, are few. We assessed the transfer incidence rate of people living with diabetes attending PHC, and the association between transfers between PHC facilities and subsequent HbA1c values. METHODS: We analysed data on HbA1c tests at public sector facilities in the Western Cape Province (2016-March 2020). Individuals with an HbA1c in 2016-2017 were followed-up for 27 months and included in the analysis if ≥18 years at first included HbA1c, ≥2 HbA1cs during follow-up and ≥1 HbA1c at a PHC facility. A visit interval was the duration between two consecutive HbA1cs. Successive HbA1cs at different facilities of any type indicated any transfer, and HbA1cs at different PHC facilities indicated a transfer between PHC facilities. Mixed effects logistic regression adjusted for sex, age, rural/urban facility attended at the start of the visit interval, disengagement (visit interval >14 months) and a hospital visit during follow-up assessed the association between transfers between PHC facilities and HbA1c >8%. RESULTS: Among 102,813 participants, 22.6% had ≥1 transfer of any type. Including repeat transfers, there were 29,994 transfers (14.4 transfers per 100 person-years, 95% confidence interval [CI] 14.3-14.6). A total of 6996 (30.1%) of those who transferred had a transfer between PHC facilities. Visit intervals with a transfer between PHC facilities were longer (349 days, interquartile range [IQR] 211-503) than those without any transfer (330 days, IQR 182-422). The adjusted relative odds of an HbA1c ≥8% after a transfer between PHC facilities versus no transfer were 1.20 (95% CI 1.05-1.37). CONCLUSION: The volume of transfers involving PHC facilities requires consideration when planning services. Individuals who transfer between PHC facilities require additional monitoring and support.

Gravity-assisted continuous flow peritoneal dialysis technique use in acute kidney injury in children: a randomized, crossover clinical trial.

BACKGROUND: Our previously demonstrated continuous flow peritoneal dialysis (CFPD) technique in children with acute kidney injury (AKI), although effective, was manpower heavy and expensive due to the high-volume pumps required. The aim of this study was to develop and test a novel gravity-driven CFPD technique in children using readily available, inexpensive equipment and to compare this technique to conventional PD. METHODS: After development and initial in vitro testing, a randomised crossover clinical trial was conducted in 15 children with AKI requiring dialysis. Patients received both conventional PD and CFPD sequentially, in random order. Primary outcomes were measures of feasibility, clearance and ultrafiltration (UF). Secondary outcomes were complications and mass transfer coefficients (MTC). Paired t-tests were used to compare PD and CFPD outcomes. RESULTS: Median (range) age and weight of participants were 6.0 (0.2-14) months and 5.8 (2.3-14.0) kg, respectively. The CFPD system was easily and rapidly assembled. There were no serious adverse events attributed to CFPD. Mean ± SD UF was significantly higher on CFPD compared to conventional PD (4.3 ± 3.15 ml/kg/h vs. 1.04 ± 1.72 ml/kg/h; p < 0.001). Clearances for urea, creatinine and phosphate for children on CFPD were 9.9 ± 3.10 ml/min/1.73 m2, 7.9 ± 3.3 ml/min/1.73 m2 and 5.5 ± 1.5 ml/min/1.73 m2 compared to conventional PD with values of 4.3 ± 1.68 ml/min/1.73 m2, 3.57 ± 1.3 ml/min/1.73 m2 and 2.53 ± 0.85 ml/min/1.73 m2, respectively (all p < 0.001). CONCLUSION: Gravity-assisted CFPD appears to be a feasible and effective way to augment ultrafiltration and clearances in children with AKI. It can be assembled from readily available non-expensive equipment. A higher resolution version of the Graphical abstract is available as Supplementary information.

From the marrow to the blood: optimising the diagnosis of iron deficiency in the setting of inflammation.

Iron deficiency (ID) is a common condition with readily available treatment but can be challenging to diagnose. Traditional biomarkers of ID are acute-phase reactants, which complicate diagnosis in patients with co-existent inflammation. This study aimed to establish optimal biomarker diagnostic thresholds for ID diagnosis using bone marrow (BM) iron stores as the gold standard and the C-reactive protein (CRP) as an inflammatory marker. A cross-sectional study was carried out in the haematology department of a tertiary academic hospital. Patients undergoing BM biopsies for any reason were recruited for inclusion. Retrospective case finding was used to enrich the data for cases with confirmed BM ID. Laboratory markers including red cell indices, reticulocyte haemoglobin and iron studies were evaluated to establish optimal cut-offs for ID diagnosis. A CRP of >5 mg/L was used as a marker of inflammation. The study included 139 patients. Forty-two had BM ID, with a median serum ferritin (SF) of 48.5 µg/L. Ninety-six of 134 (72%) had inflammation with a CRP >5 mg/L. An SF of <80 µg/L had optimal sensitivity (69%) and specificity (94%) for ID diagnosis in the whole group (odds ratio 23.5; 95% confidence interval 4.3-129). In patients without inflammation, an SF cut-off of 80 µg/L had high sensitivity (93%) and specificity (96%). An SF <200 µg/L indicated ID in those with inflammation (sensitivity 78%, specificity 74%). A transferrin saturation of <13% in those with inflammation increased the diagnostic specificity (92%). The reticulocyte haemoglobin was unhelpful in diagnosing ID in this setting. In this hospital population, SF was the best parameter to diagnose ID, even in the presence of inflammation. The CRP was useful to identify populations with inflammation in whom higher SF thresholds could be used together with the transferrin saturation to accurately diagnose ID.

Protein loss and glucose absorption in children with AKI treated with peritoneal dialysis.

BACKGROUND: Protein loss and glucose absorption in children on acute peritoneal dialysis (PD) is important to inform dietary prescription, yet data are lacking in this regard. This study was a secondary analysis of a previously published crossover randomised controlled trial, aiming to describe glucose uptake and protein loss into dialysate among children with acute kidney injury (AKI) receiving PD. METHODS: This secondary analysis described and compared dialysate albumin loss and glucose absorption in 15 children with AKI receiving PD or continuous flow peritoneal dialysis (CFPD). In addition, correlations between albumin loss, glucose absorption and other patient and dialysis factors were analysed. RESULTS: Median (range) age and weight of participants were 6.0 (0.2-14) months and 5.8 (2.3-14.0) kg, respectively. Patients received approximately 8 h of dialysis on each modality; however, results were extrapolated and expressed per day. The mean ± SD albumin loss on conventional PD and CFPD was 0.3 ± 0.19 g/kg/day and 0.56 ± 0.5 g/kg/day, respectively, and the mean ± SD glucose absorption was 4.67 ± 2.87 g/kg/day and 3.85 ±4.1 g/kg/day, respectively. There was a moderate correlation between ultrafiltration and albumin loss during CFPD only (Pearson's R = 0.61; p = 0.02). There were no significant differences between PD and CFPD for either glucose absorption or albumin loss; however, the study was not powered for this outcome. CONCLUSIONS: Protein losses and glucose absorption in children on PD with AKI are significant and should be considered when prescribing nutritional content. Protein losses on CFPD were twice as high as on conventional PD.

Comparing the effectiveness and cost-effectiveness of alternative type 2 diabetes monitoring intervals in resource limited settings.

Type 2 diabetes (T2D) represents a growing disease burden in South Africa. While glycated haemoglobin (HbA1c) testing is the gold standard for long-term blood glucose management, recommendations for HbA1c monitoring frequency are based on expert opinion. This study investigates the effectiveness and cost-effectiveness of alternative HbA1c monitoring intervals in the management of T2D. A Markov model with three health states (HbA1c <7%, HbA1c ≥ 7%, Dead) was used to estimate lifetime costs and quality-adjusted life years (QALYs) of alternative HbA1c monitoring intervals among patients with T2D, using a provider's perspective and a 3% discount rate. HbA1c monitoring strategies (three-monthly, four-monthly, six-monthly and annual tests) were evaluated with respect to the incremental cost-effectiveness ratio (ICER) assessing each comparator against a less costly, undominated alternative. The scope of costs included the direct medical costs of managing diabetes. Transition probabilities were obtained from routinely collected public sector HbA1c data, while health service utilization and health-related-quality-of-life (HRQoL) data were obtained from a local cluster randomized controlled trial. Other parameters were obtained from published studies. Robustness of findings was evaluated using one-way and probabilistic sensitivity analyses. A South African indicative cost-effectiveness threshold of USD2665 was adopted. Annual and lifetime costs of managing diabetes increased with HbA1c monitoring, while increased monitoring provides higher QALYs and life years. For the overall cohort, the ICER for six-monthly vs annual monitoring was cost-effective (USD23 22.37 per QALY gained), whereas the ICER of moving from six-monthly to three-monthly monitoring was not cost effective (USD6437.79 per QALY gained). The ICER for four-monthly vs six-monthly monitoring was extended dominated. The sensitivity analysis showed that the ICERs were most sensitive to health service utilization rates. While the factors influencing glycaemic control are multifactorial, six-monthly monitoring is potentially cost-effective while more frequent monitoring could further improve patient HrQoL.

Inflammatory markers in pregnancy are associated with postpartum weight in South African women living with HIV on antiretroviral therapy.

BACKGROUND: Postpartum weight (PPW) contributes to long-term obesity, a growing concern in persons with HIV (PWH). We investigated whether inflammatory markers in pregnancy may be involved in postpartum (PP) obesity in PWH. SETTING: A total of 57 pregnant PWH enrolled at ≤14 weeks gestation (T1) in Gugulethu antenatal care clinic in Cape Town and followed through 48 weeks PP were included. METHODS: Plasma soluble (s) CD14, sCD163, leptin, tumour necrosis factor receptor 1 (TNFR-1), resistin, adiponectin, and interleukin-6 (IL-6) were assayed in duplicate using the Luminex platform. We considered each inflammatory marker at T1 (n=57) and T3 (29-36 weeks gestation, n=31) as a separate exposure of interest. Linear mixed effects models were fit to examine whether each exposure was associated with average PPW and PPW trajectories; linear regression was used for associations with PPW change between T1 and 48 weeks. RESULTS: Median age was 32 years (IQR, 29-35), 98% were multigravida, and 49% had a BMI≥30 kg/m2. Higher T1 sCD14 levels were associated with higher average weight through 48 weeks PP (ß = 0.002, p=0.04), and T3 sCD14 with higher PPW gain (ß = 0.007, p=0.04). Leptin (ß = 0.414, p<0.01), TNFR-1 (ß = 11.048, p<0.01) and resistin (ß = 0.714, p=0.01) at T3 were associated with higher average PPW, and IL-6 (ß = 2.266, p=0.02) with PPW gain. CONCLUSION: These findings suggest that low-grade inflammation in pregnancy may play a role in postpartum obesity, pointing to potential mechanisms with implications for long-term cardiometabolic health in PWH.

Signalling cognition: the gut microbiota and hypothalamic-pituitary-adrenal axis.

Cognitive function in humans depends on the complex and interplay between multiple body systems, including the hypothalamic-pituitary-adrenal (HPA) axis. The gut microbiota, which vastly outnumbers human cells and has a genetic potential that exceeds that of the human genome, plays a crucial role in this interplay. The microbiota-gut-brain (MGB) axis is a bidirectional signalling pathway that operates through neural, endocrine, immune, and metabolic pathways. One of the major neuroendocrine systems responding to stress is the HPA axis which produces glucocorticoids such as cortisol in humans and corticosterone in rodents. Appropriate concentrations of cortisol are essential for normal neurodevelopment and function, as well as cognitive processes such as learning and memory, and studies have shown that microbes modulate the HPA axis throughout life. Stress can significantly impact the MGB axis via the HPA axis and other pathways. Animal research has advanced our understanding of these mechanisms and pathways, leading to a paradigm shift in conceptual thinking about the influence of the microbiota on human health and disease. Preclinical and human trials are currently underway to determine how these animal models translate to humans. In this review article, we summarize the current knowledge of the relationship between the gut microbiota, HPA axis, and cognition, and provide an overview of the main findings and conclusions in this broad field.

Urinary MCP-1 and TWEAK as non-invasive markers of disease activity and treatment response in patients with lupus nephritis in South Africa.

BACKGROUND: Treatment of patients with lupus nephritis (LN) requires judicious use of immunosuppression. Novel biomarkers may be useful for monitoring disease activity and treatment response. We assessed the utility of urinary monocyte chemoattractant protein-1 (uMCP-1) and urinary tumour necrosis factor-like weak inducer of apoptosis (uTWEAK) for disease activity and treatment response monitoring in South Africans with LN. METHODS: We recruited consenting patients with active LN confirmed on kidney biopsy. Urinary levels of MCP-1 and TWEAK were assayed at baseline and after completion of induction therapy using ELISA methods. We also collected relevant demographic, clinical and biochemical data for patients included in this study. RESULTS: The mean age of patients in this study was 29.8 ± 10.7 years, 60% were patients of mixed ancestry, 70% had proliferative LN and mean spot urine proteinuria at baseline was 0.37 (0.18-0.59) g/mmolCr. At completion of induction therapy, the level of uMCP-1 had reduced to 314.5 (IQR: 197.0-622) pg/mgCr from a baseline of 1092.7 (IQR 578.6-1848) pg/mgCr (P = 0.06) while uTWEAK had reduced to 36.0 (IQR 17.0-88.0) pg/mgCr from 159.0 (IQR: 88.5-295.5) pg/mgCr (P = 0.03). For patients reaching early complete or partial remission (n = 17), both biomarkers had significantly declined in their urine: uMCP-1 (P = 0.018) and uTWEAK (P = 0.015). There was no reduction of both biomarkers in patients not achieving remission and no association between uMCP-1 or uTWEAK with renal histological features. CONCLUSION: Our study shows that uMCP-1 and uTWEAK are elevated in patients with active LN, correlated with the remission status (response to treatment) at the end of induction therapy and can, therefore, be useful for monitoring disease activity and treatment response.

The First Case of Riboflavin Transporter Deficiency in sub-Saharan Africa.

This report describes the first case of a child with genetically confirmed Brown-Vialetto-van Laere syndrome in sub-Saharan Africa. This is an extremely rare clinical condition that presents with an auditory neuropathy, bulbar palsy, stridor, muscle weakness, and respiratory compromise that manifests with diaphragmatic and vocal cord paralysis. It is an autosomal recessive condition for which the genetic mutation has only recently been linked to a riboflavin transporter deficiency. We describe an 11-month-old affected male infant. He has required long-term respiratory support and a gastrostomy tube to support feeding. With high-dose riboflavin supplementation, he had limited recovery of motor function. His respiratory chain enzyme studies were abnormal suggestive of mitochondrial (mt) dysfunction. In the setting of limited resources, recognition of this striking clinical phenotype is important to highlight, specifically regarding the genetic implications of the condition and the potentially remedial response to vitamin supplementation.